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ASH 2014: BCL-2 Pathway in CLL (chronic lymphocytic leukemia)

In science and medicine, information is constantly changing and may become out-of-date as new data emerge. All articles and interviews are informational only, should never be considered medical advice, and should never be acted on without review with your health care team.

In the second part of my interview from ASH 2014 with Dr. Jeff Sharman, we learn more basic biology of the CLL cells, this time about the potent effects of leveraging the BCL-2 pathway, or life and death pathways in CLL. He wraps up with some updated data on idelalisib, and the continuing role of clinical trials.

Take Away Points

  • BCL-2 keeps CLL cells alive that might otherwise die, so blocking BCL-2 leads to a dramatic increase in cell death.
  • Too much rapid cell death can lead to a dangerous complication called tumor lysis syndrome (TLS)
  • Unlike the usual case with other oral medications, the BCL-2 blocker, ABT-199 or venetoclax can result in eliminating all disease in the blood, nodes and marrow.
  • Idelalisib and rituximab showed equal efficacy in patients with and without 17p deletion
  • More clinical trials are needed to discover the best possible drug combinations and sequences.


In this interview, Dr. Sharman explains why ABT-199 or venetoclax works so well, and the associated risk of TLS.

TLS or tumor lysis syndrome occurs when large numbers of CLL cells are killed rapidly, leading to the release of cell’s contents into the bloodstream. The kidneys and other organs are significantly challenged to cope with the amount of toxic waste produced. In the most severe cases during the early trials with ABT-199, two deaths occurred. After these tragic and sudden deaths, initial treatment doses were lowered, dosage increases were done very gradually and stringent monitoring and supportive care was instituted proving the risks of TLS can be almost completely eliminated.

Dr. Sharman also points out the impressive data with idelalisib and rituximab in the most difficult to treat patient population with deletion 17p and he discusses what trials and research is ahead of us.

Just as a reminder, Dr. Sharman has a wonderful blog well worth bookmarking.

If you didn’t catch part one, please click here.

Here is part 2 of my ASH 2014 interview with Dr. Jeff Sharman:

Brian Koffman

Volunteer Medical Director of the CLL Society